PROSTATE HEALTH

Researchers at the University of Michigan Comprehensive Center have found a potential new drug for a rare form of acute leukemia. While the drug has only been tested in the laboratory so far, they say it shows promise. After additional research on the drug, they discovered it may also play a role in the treatment of prostate cancer.

Studying Leukemia Treaments

Together, Tomasz Cierpicki, Ph.D. and Jolanta Grembecka, Ph.D. have been studying this rare form of acute leukemia in their lab for several years. They were trying to find a small-molecule inhibitor that would block the interaction between a protein called menin and MLL fusion proteins. MLL fusion proteins are known to cause this rare form of acute leukemia, called MLL fusion leukemia.

Cierpicki said: “Against all odds, we decided to explore finding a way to block the MLL-menin interaction with small molecules. From nothing, we have been able to identify and greatly improve a compound and show that it’s got valuable potential in blocking MLL fusion leukemia in animal models.”

MLL fusion leukemia is a rare type of acute leukemia that can develop in men and women of all ages. About 70 percent of people with this type of acute leukemia are children, while about 10 percent of people with this type of acute leukemia are adults. Unfortunately, the survival rate is not long because the current treatments that are available to try and treat this disease are not very effective. Only about one-third of people with MLL fusion leukemia survive longer than five years.

Lack of Effective Leukemia Treatments

Given the lack of effectiveness in available treatments, Grembecka and Cierpicki decided to investigate. They felt the protein-protein interaction between menin and MLL fusion proteins were a good interaction to study because of its role in this rare type of acute leukemia. Grembecka said: “In many types of cancer, you see multiple interactions and mutations that trigger the cancer. The MLL-menin interaction is a good drug target because it’s the primary driver in this type of leukemia. By blocking this interaction, it’s very likely to stop the cancer.”

It has been a challenge to develop drugs to inhibit protein-protein interactions like the one between menin and MLL fusion proteins. In fact, these types of protein-protein interactions such as the menin-MLL fusion protein interactions in leukemia are basically “undruggable.” Regardless, the researchers still wanted to give it a shot due to previous research they had done that showed potential hope.

In a previous study conducted by the researchers, they tested two compounds called MI-463 and MI-503, which they developed. They tested them in cell lines and in mice with MLL leukemia. What they found was that these two compounds inhibited the interaction between menin and MLL fusion proteins without doing damage to normal, healthy blood cells. These two compounds showed success because they were transferred directly into the blood and showed a high metabolic rate. This was important because in order to develop new drugs, both of these factors are essential. The study was published in the journal Cancer Cell.

The researchers had also taken the compound to the lab to try and make it potentially useful for humans, instead of just in the laboratory. By improving the pharmacologic properties as well at the potency of the drug, they were able to make it so that the compound may be able to be used in humans.

How Could Leukemia and Prostate Cancer be Connected?

So what does this drug have to do with treating prostate cancer? Well, prostate cancer researchers who also work at the University of Michigan found that menin and MLL play a role in androgen receptor signaling. Androgen receptor signaling is a driver of prostate cancer. The researchers tested the same MLL-menin inhibitors on castration resistant prostate cancer cells and mice models, which showed promise. Therefore, this research brings forward how inhibiting the protein-protein interaction between menin and MLL may have the potential to treat prostate cancer. The study was published in the journal Nature Medicine.

Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational and the senior author on the Nature Medicine paper said: “Our study suggests that this MLL-menin inhibitor might also have a potential role in a more common solid tumor, in this case prostate cancer.”

While this new research is exciting as it could be useful in treating two very serious diseases, the compounds do require additional testing in the lab. Until then, there will not be any clinical trials to test the compounds on humans. Both Grembecka and Cierpicki are working to further develop their findings in order to get the compounds into clinical trials, and Chinnaiyan is working to further study and test the compound’s role in treating prostate cancer.